Age related changes in the immune system are to be investigated. Specifically, the age related changes in the susceptibility to the induction and termination of acquired immunological tolerance to human immunoglobulin in long- and short-lived strains of mice will be investigated. The mechanisms of the increased incidence of autoimmunity which occurs with advancing age will be investigated using the murine thyroiditis models in which the autoimmune lesion is induced with cross reacting thyroglobulins. These studies have shown that mice become more resistant to tolerance induction with advancing age and that the tolerant state is of short duration in old mice. Long-lived mice which, as young adults, are more susceptible to tolerance induction become markedly more resistant with advancing age. Their susceptibility becomes more like that of the short-lived strains.